Luis G. Paz-Ares, MD, PhD, on IMforte Trial in Extensive-Stage SCLC

I presented at ASCO this year the results of the IMforte trial. This is a randomized phase 3 study of the combination of lurbinectedin plus atezolizumab versus atezolizumab alone as first-line maintenance treatment for patients with extensive-stage small cell lung cancer. There is a clear need to improve the efficacy of those regimens in the first-line setting. Currently, chemoimmunotherapy provides responses to most patients, but relapses typically happen very early on, and long-term survival is a rare event. Our group has shown the synergistic effect in immunocompetent models of lurbinectedin plus atezolizumab, and we have previously conducted phase 1 and phase 2 trials. We showed that this combination is feasible in the clinic at full doses with a predictable safety profile and encouraging activity. Therefore, we developed this phase 3 trial where patients with extensive-stage small cell lung cancer, previously untreated and without brain metastases, were treated with four courses of induction treatment with carboplatin, etoposide, and atezolizumab. Only those patients who had a response or disease stabilization and still had a good performance status were randomized in the maintenance phase, which is the randomized portion of the study. Patients were randomized in a 1:1 fashion to receive either the standard of care maintenance with atezolizumab or the experimental arm with lurbinectedin plus atezolizumab. The primary endpoints were progression-free survival (PFS) by an independent review facility and overall survival (OS). A total of 483 patients were included. Patient characteristics were typical of those seen in similar phase 3 studies and were balanced. The PFS primary endpoint by an independent review facility was clearly superior for patients treated with the combination, with a hazard ratio of 0.54, which was statistically significant with a p-value of 0.0001. That translated into an increase in median PFS from 2.1 to 5.4 months in patients treated with the combination. When PFS was assessed by investigators, the results were consistent, and we appreciated the benefit across all relevant subgroup analyses included in the trial. The second primary endpoint, OS, showed similar results and improvement that was statistically significant with a hazard ratio of 0.73 in favor of the combination, with a p-value of 0.0174. That translated into an increase in median OS from 10.6 to 13.2 months. In terms of response, the data were consistent, and we appreciated an increase in the number of side effects with the combination as expected, but the toxicity profile was predictable, manageable, and very few patients required discontinuation—6% compared to 3% with atezolizumab alone. Hematological toxicity was more common, but we did not observe bleeding events, febrile neutropenia, and the infection rate was similar in the two arms. Altogether, we can conclude that this trial shows a statistically significant and clinically relevant improvement in PFS and OS for patients treated with lurbinectedin plus atezolizumab compared to atezolizumab alone. The safety profile was predictable, with an increase in some side effects that were typically low grade, low discontinuation rate, and all events were resolved. We believe that lurbinectedin plus atezolizumab may become a new standard of care for patients in first-line maintenance for extensive-stage small cell lung cancer.